Environmental Toxicology最新文献

{"title":"Subchronic Chloroform Exposure Causes Intestinal Damage and Induces Gut Microbiota Disruption and Metabolic Dysregulation in Mice","authors":"Zaishan Wang,&nbsp;Meng Xu,&nbsp;Qiang Li,&nbsp;Sihan Lu,&nbsp;Zhu Liu","doi":"10.1002/tox.24417","DOIUrl":"10.1002/tox.24417","url":null,"abstract":"<div>\u0000 \u0000 <p>Chloroform is a prevalent toxic environmental pollutant in urban settings, posing risks to human health through exposure via various mediums such as air and tap water. The gut microbiota plays a pivotal role in maintaining host health. However, there is a paucity of research elucidating the impact of chloroform exposure on the gut microbiota. In this investigation, 18 SPF Kunming female mice were stratified into three groups (<i>n</i> = 6) and subjected to oral gavage with chloroform doses equivalent to 0, 50, and 150 mg/kg of body weight over 30 days. Our findings demonstrate that subchronic chloroform exposure significantly perturbs hematological parameters in mice and induces histopathological alterations in cecal tissues, consequently engendering marked disparities in the functional composition of cecal microbiota and metabolic equilibrium of cecal contents. Ultimately, our investigation revealed a statistically robust correlation, exhibiting a high degree of significance, between the intestinal microbiome composition and the metabolites that were differentially expressed consequent to chloroform exposure.</p>\u0000 </div>","PeriodicalId":11756,"journal":{"name":"Environmental Toxicology","volume":"40 1","pages":"5-18"},"PeriodicalIF":4.4,"publicationDate":"2024-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142105569","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Blocking IL-23 Signaling Mitigates Cigarette Smoke-Induced Murine Emphysema","authors":"Xue Tian,&nbsp;Shaohua Wang,&nbsp;Chujie Zhang,&nbsp;Y. S. Prakash,&nbsp;Robert Vassallo","doi":"10.1002/tox.24405","DOIUrl":"10.1002/tox.24405","url":null,"abstract":"<div>\u0000 \u0000 <p>Inflammatory cell infiltration is a characteristic feature of COPD and correlates directly with the severity of the disease. Interleukin-23 (IL-23) is a pro-inflammatory cytokine that regulates Th-17 inflammation, which mediates many pathophysiological events in COPD. The primary goal of this study was to determine the role of IL-23 as a mediator of key pathologic processes in cigarette smoke-induced COPD. In this study, we report an increase in <i>IL23</i> gene expression in the lung biopsies of COPD patients compared to controls and identified a positive correlation between <i>IL23</i> gene expression and disease severity. In a cigarette smoke-induced murine emphysema model, the suppression of IL-23 with a monoclonal blocking antibody reduced the severity of cigarette smoke-induced murine emphysema. Mechanistically, the suppression of IL-23 was associated with a reduction in immune cell infiltration, oxidative stress injury, and apoptosis, suggesting a role for IL-23 as an essential immune mediator of the inflammatory processes in the pathogenesis of CS-induced emphysema.</p>\u0000 </div>","PeriodicalId":11756,"journal":{"name":"Environmental Toxicology","volume":"39 12","pages":"5334-5346"},"PeriodicalIF":4.4,"publicationDate":"2024-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142105568","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Epigenetic Regulation of RNF135 by LSD1 Promotes Stemness Maintenance and Brain Metastasis in Lung Adenocarcinoma","authors":"Xiaohan Qu,&nbsp;Tianjian Ding,&nbsp;Haoqi Zhao,&nbsp;Liming Wang","doi":"10.1002/tox.24407","DOIUrl":"10.1002/tox.24407","url":null,"abstract":"<div>\u0000 \u0000 <p>RING finger protein 135 (RNF135) is identified as a regulator in certain cancer types. However, its role and molecular mechanisms in lung adenocarcinoma (LUAD) are still unclear. Herein, we investigated the level of RNF135 in tumor tissues of LUAD patients using the UALCAN database and confirmed the data by real-time PCR and western blot analysis. The effects of RNF135 on stemness maintenance and migration/invasion capability of LUAD cells were investigated by sphere formation, flow cytometry, wound healing, and transwell assay. Limiting dilution xenograft assay and intracardiac injection of LUAD cells were applied to assess the implications of RNF135 in tumorigenesis and brain metastasis. Our results revealed that RNF135 was upregulated in tumor tissues of LUAD patients and was positively correlated with poor prognosis. Knockdown of RNF135 suppressed cancer stem cells (CSCs)-like properties, and migration/invasion capability of A549 and NCI-H1975 cells. Conversely, overexpression of RNF135 augmented CSCs-like traits and migration/invasion ability of LUAD cells. Limiting dilution xenograft assay demonstrated that RNF135 was required for the self-renewal of CSCs to initiate LUAD development. Overexpression of RNF135 in A549 cells increased their ability to metastasize to the brain in vivo. Mechanistically, the transcriptional activation of RNF135 by LSD1 involved H3K9me2 demethylation at the promoter region of RNF135. Reexpression of RNF135 in LSD1-silenced A549 cells was able to reverse LSD1-mediated stemness maintenance and migration/invasion capability. Overall, our results implied that targeting of LSD1/RNF135 axis might be a feasible method to suppress tumorigenesis and brain metastasis of LUAD patients.</p>\u0000 </div>","PeriodicalId":11756,"journal":{"name":"Environmental Toxicology","volume":"39 12","pages":"5321-5333"},"PeriodicalIF":4.4,"publicationDate":"2024-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142101434","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Increased Apoptosis of Mesenchymal Stem Cells Mediated Osteopenia Due to Prenatal Nicotine Exposure in Female Offspring Rats via IGF1 Pathway","authors":"Xufeng Li,&nbsp;Hao Xiao,&nbsp;Zhixin Wu,&nbsp;Hui Wang,&nbsp;Liaobin Chen","doi":"10.1002/tox.24391","DOIUrl":"10.1002/tox.24391","url":null,"abstract":"<div>\u0000 \u0000 <p>Nicotine exposure is a common adverse environment during pregnancy and causes developmental toxicity of long bones in offspring. However, the effect of prenatal nicotine exposure (PNE) on bone mass accumulation in female offspring and its mechanism remained to be further investigated. In this study, we constructed a PNE rat model and collected the long bone and the bone marrow mesenchymal stem cells (BMSCs) from female offspring rats for the detection of bone mass, cell apoptosis, and the expressions of osteogenesis- and apoptosis-related genes. The results revealed that PNE induced low bone mass in female offspring rats and was associated with the suppression of osteogenic function. Moreover, the apoptosis of BMSCs derived from the PNE female offspring rats was raised, and the expression ratio of apoptosis marker genes BAX/BCL-2 was significantly increased. Further, PNE inhibited the expression and function of insulin-like growth factor l (IGF1) signaling pathway in BMSCs. However, the exogenous IGF1 treatment partially ameliorated the increased apoptosis of BMSCs derived from the PNE female offspring rats. In conclusion, PNE induced low bone mass in female offspring rats, which was attributed to the increased apoptosis of BMSCs due to functional inhibition of IGF1 signaling pathway.</p>\u0000 </div>","PeriodicalId":11756,"journal":{"name":"Environmental Toxicology","volume":"39 11","pages":"5199-5208"},"PeriodicalIF":4.4,"publicationDate":"2024-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142101226","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Picrasidine I Regulates Apoptosis in Melanoma Cell Lines by Activating ERK and JNK Pathways and Suppressing AKT Signaling","authors":"Mu-Kuei Shieu,&nbsp;Chia-Chieh Lin,&nbsp;Hsin-Yu Ho,&nbsp;Yu-Sheng Lo,&nbsp;Yi-Ching Chuang,&nbsp;Ming-Ju Hsieh","doi":"10.1002/tox.24404","DOIUrl":"10.1002/tox.24404","url":null,"abstract":"<p>World Health Organization data indicate a continuous increase in melanoma incidence, with metastatic melanoma characterized by poor prognosis and drug resistance. The exploration of therapeutics derived from natural products remains an active area of in vitro research. The aim of this study was to determine the antitumor effects of picrasidine I, a natural compound extracted from <i>Picrasma quassioides</i>, against two melanoma cell lines. We selected two metastatic melanoma cell lines, HMY-1 and A2058, for molecular studies, including Western blotting, 4′,6-diamidino-2-phenylindole staining, and flow cytometry. Picrasidine I demonstrated cytotoxic effects against the HMY-1 and A2058 melanoma cell lines. It induced cell cycle arrest in the sub-G1 phase and downregulated cell cycle–related proteins (e.g., cyclin A2, D1, cyclin-dependent kinases 4, and 6). In the intrinsic apoptosis pathway, picrasidine I activated proapoptotic proteins (e.g., Bax, Bak, t-Bid, BimL/S) and suppressed the expression of antiapoptotic proteins (e.g., Bcl-2, Bcl-xL), with an observed increase in the quantity of depolarized cells. In addition, the apoptotic effects of picrasidine I were linked to the activation of the c-Jun <i>N</i>-terminal kinase and extracellular signal-regulated kinase pathways and the inhibition of the protein kinase B signaling pathway. A human apoptosis array indicated claspin inhibition upon picrasidine I treatment, suggesting the potential involvement of picrasidine I in apoptosis and cell cycle regulation. Our findings suggest that picrasidine I has potential as a candidate for treating advanced melanoma, and thus these findings warrant further investigation. The modulation of claspin expression by picrasidine I could be investigated further as a potential biomarker to predict its efficacy in related to advanced stages of melanoma.</p>","PeriodicalId":11756,"journal":{"name":"Environmental Toxicology","volume":"39 12","pages":"5309-5320"},"PeriodicalIF":4.4,"publicationDate":"2024-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/tox.24404","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142079643","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Subway Fine Particles (PM2.5)-Induced Pro-Inflammatory Response Triggers Airway Epithelial Barrier Damage Through the TLRs/NF-κB-Dependent Pathway In Vitro","authors":"Fanmei Zeng,&nbsp;Guanhua Pang,&nbsp;Liwen Hu,&nbsp;Yuan Sun,&nbsp;Wen Peng,&nbsp;Yuwei Chen,&nbsp;Dan Xu,&nbsp;Qing Xia,&nbsp;Luwei Zhao,&nbsp;Yifei Li,&nbsp;Miao He","doi":"10.1002/tox.24403","DOIUrl":"10.1002/tox.24403","url":null,"abstract":"<div>\u0000 \u0000 <p>Subways are widely used in major cities around the world, and subway fine particulate matter (PM_2.5) is the main source of daily PM_2.5 exposure for urban residents. Exposure to subway PM_2.5 leads to acute inflammatory damage in humans, which has been confirmed in mouse in vivo studies. However, the concrete mechanism by which subway PM_2.5 causes airway damage remains obscure. In this study, we found that subway PM_2.5 triggered release of pro-inflammatory cytokines such as interleukin 17E, tumor necrosis factor α, transforming growth factor β, and thymic stromal lymphopoietin from human bronchial epithelial cells (BEAS-2B) in a dose–effect relationship. Subsequently, supernatant recovered from the subway PM_2.5 group significantly increased expression of the aforementioned cytokines in BEAS-2B cells compared with the subway PM_2.5 group. Additionally, tight junctions (TJs) of BEAS-2B cells including zonula occludens-1, E-cadherin, and occludin were decreased by subway PM_2.5 in a dose-dependent manner. Moreover, supernatant recovered from the subway PM_2.5 group markedly decreased the expression of these TJs compared with the control group. Furthermore, inhibitors of toll-like receptors (TLRs) and nuclear factor-kappa B (NF-κB), as well as chelate resins (e.g., chelex) and deferoxamine, remarkably ameliorated the observed changes of cytokines and TJs caused by subway PM_2.5 in BEAS-2B cells. Therefore, these results suggest that subway PM_2.5 induced a decline of TJs after an initial ascent of cytokine expression, and subway PM_2.5 altered expression of both cytokines and TJs by activating TLRs/NF-κB-dependent pathway in BEAS-2B cells. The metal components of subway PM_2.5 may contribute to the airway epithelial injury.</p>\u0000 </div>","PeriodicalId":11756,"journal":{"name":"Environmental Toxicology","volume":"39 12","pages":"5296-5308"},"PeriodicalIF":4.4,"publicationDate":"2024-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142072256","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction to “Endoplasmic Reticulum Chaperone GRP78 Participates in Fluoride-Induced Autophagy in LS8 Cells by Regulating the IRE1-TRAF2-JNK Pathway”","authors":"","doi":"10.1002/tox.24402","DOIUrl":"10.1002/tox.24402","url":null,"abstract":"<p>L. Zhao, L. Wang, H. Wang, et al., “Endoplasmic Reticulum Chaperone GRP78 Participates in Fluoride-Induced Autophagy in LS8 Cells by Regulating the IRE1-TRAF2-JNK Pathway,” <i>Environmental Toxicology</i> 38, no. 7 (2023): 1756–1767.</p><p>We have discovered that there is a duplication of the Western Blot (WB) images of Beclin1 in Figure 2, panels A and E. Upon reviewing our experimental data, we found that the error occurred during the copying pictures process. However, we have cross-checked our results, and the statistical data is accurate. Only the image copying process has errors. Now we provide the three experimental results of WB images of Beclin1 from Figure 2, panels A, E, and I, along with the corrected results, for your review.</p><p>After modification</p>","PeriodicalId":11756,"journal":{"name":"Environmental Toxicology","volume":"40 1","pages":"152-153"},"PeriodicalIF":4.4,"publicationDate":"2024-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/tox.24402","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142072255","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sudachitin Alleviates Paraquat Instigated Testicular Toxicity in Albino Rats via Regulating Nrf-2/Keap-1, Inflammatory, Steroidogenic, and Histological Profile","authors":"Muhammad Umar Ijaz,&nbsp;Sana Imtiaz,&nbsp;Muhammad Faisal Hayat,&nbsp;Moazama Batool,&nbsp;Khalid A. Al-Ghanim,&nbsp;Mian Nadeem Riaz","doi":"10.1002/tox.24408","DOIUrl":"10.1002/tox.24408","url":null,"abstract":"<div>\u0000 \u0000 <p>Paraquat (PQ) is a noxious herbicide which adversely affects the vital organs including male reproductive system. Sudachitin (SCN) is a naturally occurring flavonoid that demonstrates a wide range of biological potentials. The current study was designed to investigate the alleviative potential of SCN to avert PQ-induced testicular toxicity in rats. Forty-eight male rats (<i>Rattus norvegicus</i>) were apportioned into four groups including control, PQ (5 mg/kg), PQ + SCN (5 mg/kg + 30 mg/kg), and SCN (30 mg/kg) only treated group. Our findings elucidated that PQ treatment reduced the expression of nuclear factor erythroid 2-related factor 2 (Nrf-2) and its antioxidant genes as well as the activities of superoxide dismutase (SOD), catalase (CAT), glutathione reductase (GSR) and glutathione peroxidase (GPx), while elevating the levels of reactive oxygen species (ROS), and malondialdehyde (MDA). Furthermore, PQ intoxication upregulated the expressions of Keap-1 while downregulating the expression of 3-beta hydroxysteroid dehydrogenase (3β-HSD), 17-beta hydroxysteroid dehydrogenase (17β-HSD), and steroidogenic acute regulatory protein (StAR). Moreover, sperm anomalies were increased following the exposure to PQ. Besides, PQ exposure decreased the levels of plasma testosterone, luteinizing hormone (LH), and follicle stimulating hormone (FSH) while increasing the levels of interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), nuclear factor-kappa B (NF-κB), interleukin-1beta (IL-1β), and cyclooxygenase-2 (COX-2). Additionally, PQ treatment escalated the expressions of cysteinyl aspartate-specific proteases-3 (Caspase-3) and Bcl-2-associated X-protein (Bax) while downregulating the expressions of B-cell lymphoma-2 (Bcl-2). Furthermore, PQ exposure disrupted the normal architecture of testicular tissues. However, SCN treatment remarkably protected the testicular tissues via regulating the aforementioned disruptions owing to its antioxidant, anti-inflammatory, and androgenic potential.</p>\u0000 </div>","PeriodicalId":11756,"journal":{"name":"Environmental Toxicology","volume":"39 12","pages":"5284-5295"},"PeriodicalIF":4.4,"publicationDate":"2024-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142046519","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"PEITC Induces DNA Damage and Inhibits DNA Repair-Associated Proteins in Human Retinoblastoma Cells In Vitro","authors":"Sheng-Yao Hsu,&nbsp;Yi-Ping Huang,&nbsp;Te-Chun Hsia,&nbsp;Jaw-Chyun Chen,&nbsp;Shu-Fen Peng,&nbsp;Wen-Tsong Hsieh,&nbsp;Fu-Shin Chueh,&nbsp;Chao-Lin Kuo","doi":"10.1002/tox.24393","DOIUrl":"10.1002/tox.24393","url":null,"abstract":"<div>\u0000 \u0000 <p>Phenethyl isothiocyanate (PEITC), a natural product, exists in biological activities, including anticancer activity in many human cancer cells. No information shows that PEITC affects DNA damage in human retinoblastoma (RB) cells in vitro. In this study, the aim of experiments was to determine whether PEITC decreased total viable cell number or not by inducing protein expressions involved in DNA damage and repair in Y79 RB cells in vitro. Total cell viability was measured by PI exclusion assay, and PEITC reduced the total Y79 viable cell numbers in a dose-dependent manner. DNA condensation and DNA impairment were conducted by DAPI staining and comet assays, respectively, in Y79 cells. The findings show that PEITC induced DNA condensation dose-dependently based on the brighter fluorescence of cell nuclei stained by DAPI staining. PEITC-induced DNA damage showed a more extended DNA migration smears than that of the control, which was performed by a comet assay. Western blotting was performed to measure the protein expressions involved in DNA damage and repair, which showed that PEITC at 2.5–10 μM increased NRF2, HO-1, SOD (Mn), and catalase; however, it decreased SOD (Cu/Zn) except 10 μM PEITC treatment, and decreased glutathione, which were associated with oxidative stress. Furthermore, PEITC increased DNA-PK, MDC1, H₂A.X^pSer139, ATM^pSer1981, p53, p53^pSer15, PARP, HSP70, and HSP90, but decreased TOPIIα, TOPIIβ, and MDM2^pSer166 that were associated with DNA damage and repair mechanism in Y79 cells. The examination from confocal laser microscopy shows that PEITC increased H₂A.X^pSer139 and p53^pSer15, and decreased glutathione and TOPIIα in Y79 cells. In conclusion, the cytotoxic effects of PEITC on reducing the number of viable cells may be due to the induction of DNA damage and the alteration of DNA repair proteins in Y79 cells in vitro.</p>\u0000 </div>","PeriodicalId":11756,"journal":{"name":"Environmental Toxicology","volume":"39 12","pages":"5274-5283"},"PeriodicalIF":4.4,"publicationDate":"2024-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142035482","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Anti-Metastatic Action of Oxyresveratrol via Suppression of Phosphoryl-ERK/-PKCα-Mediated Sp1/MMP1 Signaling in Human Renal Carcinoma Cells","authors":"Tsai-Kun Wu,&nbsp;Yi-Hsien Hsieh,&nbsp;Tung-Wei Hung,&nbsp;Yi-Chen Lin,&nbsp;Chia-Liang Lin,&nbsp;Yu-Jou Liu,&nbsp;Ying-Ru Pan,&nbsp;Jen-Pi Tsai","doi":"10.1002/tox.24400","DOIUrl":"10.1002/tox.24400","url":null,"abstract":"<div>\u0000 \u0000 <p>Oxyresveratrol (OxyR) exerts biological and pharmacological effects in a variety of tumor cells, including antioxidant action, antitumor activity, and proapoptotic effects. However, the regulation of targeted signaling pathways by OxyR and the mechanism underlying these effects in human renal cell carcinoma (RCC) have been less studied. We observed that OxyR at noncytotoxic doses did not affect the growth of human RCC cells or normal kidney HK2 cells. OxyR inhibited ACHN and Caki-1 cell migration and invasion through targeting matrix metalloproteinase 1 (MMP1) expression. Analysis of clinical databases showed that high MMP1 expression is associated with lower overall survival (OS) in these cancers (<i>p</i> &lt; 0.01). OxyR significantly inhibited the mRNA and protein expression of Sp1. Furthermore, luciferase assay results showed that OxyR inhibited Sp1 transcriptional activity. Additionally, OxyR preferentially suppressed the activation of ERK and PKCα. Treatment with U0126 (MEK inhibitor) or G06976 (PKCα inhibitor) clearly decreased Sp1 and MMP1 expression and inhibited RCC cell migration and invasion. In conclusion, OxyR may be a potential antitumor therapy for the inhibition of migration and invasion by controlling p-ERK/Sp1 and p-PKCα/Sp1-mediated MMP1 expression in RCC.</p>\u0000 </div>","PeriodicalId":11756,"journal":{"name":"Environmental Toxicology","volume":"39 12","pages":"5264-5273"},"PeriodicalIF":4.4,"publicationDate":"2024-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142016774","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}